Activation of epigenetic regulator KDM6B by Salmonella Typhimurium enables chronic infections

Non-typhoidal Salmonella (NTS) infections result in self limiting gastroenteritis except in rare cases wherein manifestations of chronic infections can occur. Strategies employed by Salmonella to thrive in hostile environments of host during chronic infections are complex and multifaceted. In chroni...

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Autores principales:	Sarika Rana, Sonalika Maurya, Gayatree Mohapatra, Savita Singh, Rohan Babar, Hridya Chandrasekhar, Garima Chamoli, Deepak Rathore, Pallavi Kshetrapal, C. V. Srikanth
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	salmonella typhimurium kdm6b h3k27me3 chronic infection pparδ spi1 effectors Diseases of the digestive system. Gastroenterology RC799-869
Acceso en línea:	https://doaj.org/article/1dcc23419112498fa40bba43a59ddbcf
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spelling	oai:doaj.org-article:1dcc23419112498fa40bba43a59ddbcf2021-11-04T15:00:42ZActivation of epigenetic regulator KDM6B by Salmonella Typhimurium enables chronic infections1949-09761949-098410.1080/19490976.2021.1986665https://doaj.org/article/1dcc23419112498fa40bba43a59ddbcf2021-01-01T00:00:00Zhttp://dx.doi.org/10.1080/19490976.2021.1986665https://doaj.org/toc/1949-0976https://doaj.org/toc/1949-0984Non-typhoidal Salmonella (NTS) infections result in self limiting gastroenteritis except in rare cases wherein manifestations of chronic infections can occur. Strategies employed by Salmonella to thrive in hostile environments of host during chronic infections are complex and multifaceted. In chronic state, a coordinated action of bacterial effectors allows reprogramming of macrophages to M2 subtype and thereby creating a permissible replicative niche. The mechanistic details of these processes are not fully known. In the current study we identified, histone H3-lysine 27 trimethylation (H3K27me3)-specific demethylase, KDM6B to be upregulated in both cell culture and in murine model of Salmonella infection. KDM6B recruitment upon infection exhibited an associated loss of overall H3K27me3 in host cells and was Salmonella SPI1 effectors coordinated. ChIP-qRT-PCR array analysis revealed several new gene promoter targets of KDM6B demethylase activity including PPARδ, a crucial regulator of fatty acid oxidation pathway and Salmonella-persistent infections. Furthermore, pharmacological inhibition of KDM6B demethylase activity with GSKJ4 in chronic Salmonella infection mice model led to a significant reduction in pathogen load and M2 macrophage polarization in peripheral lymphoid organs. The following work thus reveals Salmonella effector-mediated epigenetic reprogramming of macrophages responsible for its long-term survival and chronic carriage.Sarika RanaSonalika MauryaGayatree MohapatraSavita SinghRohan BabarHridya ChandrasekharGarima ChamoliDeepak RathorePallavi KshetrapalC. V. SrikanthTaylor & Francis Grouparticlesalmonella typhimuriumkdm6bh3k27me3chronic infectionpparδspi1 effectorsDiseases of the digestive system. GastroenterologyRC799-869ENGut Microbes, Vol 13, Iss 1 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	salmonella typhimurium kdm6b h3k27me3 chronic infection pparδ spi1 effectors Diseases of the digestive system. Gastroenterology RC799-869
spellingShingle	salmonella typhimurium kdm6b h3k27me3 chronic infection pparδ spi1 effectors Diseases of the digestive system. Gastroenterology RC799-869 Sarika Rana Sonalika Maurya Gayatree Mohapatra Savita Singh Rohan Babar Hridya Chandrasekhar Garima Chamoli Deepak Rathore Pallavi Kshetrapal C. V. Srikanth Activation of epigenetic regulator KDM6B by Salmonella Typhimurium enables chronic infections
description	Non-typhoidal Salmonella (NTS) infections result in self limiting gastroenteritis except in rare cases wherein manifestations of chronic infections can occur. Strategies employed by Salmonella to thrive in hostile environments of host during chronic infections are complex and multifaceted. In chronic state, a coordinated action of bacterial effectors allows reprogramming of macrophages to M2 subtype and thereby creating a permissible replicative niche. The mechanistic details of these processes are not fully known. In the current study we identified, histone H3-lysine 27 trimethylation (H3K27me3)-specific demethylase, KDM6B to be upregulated in both cell culture and in murine model of Salmonella infection. KDM6B recruitment upon infection exhibited an associated loss of overall H3K27me3 in host cells and was Salmonella SPI1 effectors coordinated. ChIP-qRT-PCR array analysis revealed several new gene promoter targets of KDM6B demethylase activity including PPARδ, a crucial regulator of fatty acid oxidation pathway and Salmonella-persistent infections. Furthermore, pharmacological inhibition of KDM6B demethylase activity with GSKJ4 in chronic Salmonella infection mice model led to a significant reduction in pathogen load and M2 macrophage polarization in peripheral lymphoid organs. The following work thus reveals Salmonella effector-mediated epigenetic reprogramming of macrophages responsible for its long-term survival and chronic carriage.
format	article
author	Sarika Rana Sonalika Maurya Gayatree Mohapatra Savita Singh Rohan Babar Hridya Chandrasekhar Garima Chamoli Deepak Rathore Pallavi Kshetrapal C. V. Srikanth
author_facet	Sarika Rana Sonalika Maurya Gayatree Mohapatra Savita Singh Rohan Babar Hridya Chandrasekhar Garima Chamoli Deepak Rathore Pallavi Kshetrapal C. V. Srikanth
author_sort	Sarika Rana
title	Activation of epigenetic regulator KDM6B by Salmonella Typhimurium enables chronic infections
title_short	Activation of epigenetic regulator KDM6B by Salmonella Typhimurium enables chronic infections
title_full	Activation of epigenetic regulator KDM6B by Salmonella Typhimurium enables chronic infections
title_fullStr	Activation of epigenetic regulator KDM6B by Salmonella Typhimurium enables chronic infections
title_full_unstemmed	Activation of epigenetic regulator KDM6B by Salmonella Typhimurium enables chronic infections
title_sort	activation of epigenetic regulator kdm6b by salmonella typhimurium enables chronic infections
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/1dcc23419112498fa40bba43a59ddbcf
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Activation of epigenetic regulator KDM6B by Salmonella Typhimurium enables chronic infections

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